Genetic barriers more than environmental associations explain Serratia marcescens population structure.

Bacterial species often comprise well-separated lineages, likely emerged and maintained by genetic isolation and/or ecological divergence. How these two evolutionary actors interact in the shaping of bacterial population structure is currently not fully understood. In this study, we investigate the genetic and ecological drivers underlying the evolution of Serratia marcescens, an opportunistic pathogen with high genomic flexibility and able to colonise diverse environments. Comparative genomic analyses reveal a population structure composed of five deeply-demarcated genetic clusters with open pan-genome but limited inter-cluster gene flow, partially explained by Restriction-Modification (R-M) systems incompatibility. Furthermore, a large-scale research on hundred-thousands metagenomic datasets reveals only a partial habitat separation of the clusters. Globally, two clusters only show a separate gene composition coherent with ecological adaptations. These results suggest that genetic isolation has preceded ecological adaptations in the shaping of the species diversity, an evolutionary scenario coherent with the Evolutionary Extended Synthesis.

Cultivation and sequencing-free protocol for Serratia marcescens detection and typing.

Serratia marcescens is an opportunistic pathogen that survives in inhospitable environments causing large outbreaks, particularly in neonatal intensive care units (NICUs). Genomic studies revealed that most S. marcescens nosocomial infections are caused by a specific clone (here "Infectious clone"). Whole genome sequencing (WGS) is the only portable method able to identify this clone, but it requires days to obtain results. We present a cultivation-free hypervariable-locus melting typing (HLMT) protocol for the fast detection and typing of S. marcescens, with 100% detection capability on mixed samples and a limit of detection that can reach the 10 genome copies. The protocol was able to identify the S. marcescens infectious clone with 97% specificity and 96% sensitivity when compared to WGS, yielding typing results portable among laboratories. The protocol is a cost and time saving method for S. marcescens detection and typing for large environmental/clinical surveillance screenings, also in low-middle income countries.

The emergence and diversification of a zoonotic pathogen from within the microbiota of intensively farmed pigs.

The expansion and intensification of livestock production is predicted to promote the emergence of pathogens. As pathogens sometimes jump between species, this can affect the health of humans as well as livestock. Here, we investigate how livestock microbiota can act as a source of these emerging pathogens through analysis of Streptococcus suis, a ubiquitous component of the respiratory microbiota of pigs that is also a major cause of disease on pig farms and an important zoonotic pathogen. Combining molecular dating, phylogeography, and comparative genomic analyses of a large collection of isolates, we find that several pathogenic lineages of S. suis emerged in the 19th and 20th centuries, during an early period of growth in pig farming. These lineages have since spread between countries and continents, mirroring trade in live pigs. They are distinguished by the presence of three genomic islands with putative roles in metabolism and cell adhesion, and an ongoing reduction in genome size, which may reflect their recent shift to a more pathogenic ecology. Reconstructions of the evolutionary histories of these islands reveal constraints on pathogen emergence that could inform control strategies, with pathogenic lineages consistently emerging from one subpopulation of S. suis and acquiring genes through horizontal transfer from other pathogenic lineages. These results shed light on the capacity of the microbiota to rapidly evolve to exploit changes in their host population and suggest that the impact of changes in farming on the pathogenicity and zoonotic potential of S. suis is yet to be fully realized.

Precision Genome Engineering in Streptococcus suis Based on a Broad-Host-Range Vector and CRISPR-Cas9 Technology.

Streptococcussuis is an important zoonotic pathogen that causes severe invasive disease in pigs and humans. Current methods for genome engineering of S. suis rely on the insertion of antibiotic resistance markers, which is time-consuming and labor-intensive and does not allow the precise introduction of small genomic mutations. Here we developed a system for CRISPR-based genome editing in S. suis, utilizing linear DNA fragments for homologous recombination (HR) and a plasmid-based negative selection system for bacteria not edited by HR. To enable the use of this system in other bacteria, we engineered a broad-host-range replicon in the CRISPR plasmid. We demonstrated the utility of this system to rapidly introduce multiple gene deletions in successive rounds of genome editing and to make precise nucleotide changes in essential genes. Furthermore, we characterized a mechanism by which S. suis can escape killing by a targeted Cas9-sgRNA complex in the absence of HR. A characteristic of this new mechanism is the presence of very slow-growing colonies in a persister-like state that may allow for DNA repair or the introduction of mutations, alleviating Cas9 pressure. This does not impact the utility of CRISPR-based genome editing because the escape colonies are easily distinguished from genetically edited clones due to their small colony size. Our CRISPR-based editing system is a valuable addition to the genetic toolbox for engineering of S. suis, as it accelerates the process of mutant construction and simplifies the removal of antibiotic markers between successive rounds of genome editing.

Multigenerational effects of the insecticide Pyriproxyfen and recovery in Daphnia magna.

In the present study, an ecotoxicological approach to the evaluation of the insecticide Pyriproxifen in the crustacean Daphnia magna was done. Acute toxicity tests (48 h), feeding behavior test (5 h) and chronic toxicity test (21 days) were carried out on a parental daphnid generation (F0). Pyriproxifen D. magna EC50 value in our experimental conditions was 336.47 µg/L. Based on this result, sublethal test concentrations were selected for the feeding study and the F0 chronic experiment. Filtration and ingestion rates of D. magna exposed animals did not show any significant difference respect to control daphnids. However, daphnids from the parental F0 generation when exposed to the insecticide during 21 days showed a decreased in all the reproductive parameters tested (mean total neonates per female, mean brood size, time to first brood, and mean number of broods per female) as well as in the population statistic growth rate (r), although survival was not affected. On the other hand, offspring from F0 females exposed to the highest Pyriproxifen concentration (14.02 µg/L) were separated in two F1 generation experiments. One group was transferred during 21 days to a medium free of toxicant (F1 generation-TC group) while the other group was exposed during 21 days to the same insecticide concentration as their mothers (14.02 µg/L) (F1 generation-TT group). Results from both experiments determined a decreased in most of the reproductive parameters which was higher in the F1-TT group, although some of them were recovered in the F1-TC group. On the other hand, the morphological analysis of the daphnids showed that the coloration pattern was altered in the daphnids exposed to the insecticide, together with a significant size decreased, and neonates from F0 progeny with the same morphological abnormality. Finally, we determined that the insecticide caused the appearance of males among the offspring generated by the F0.

Changes in the oral status and periodontal pathogens in a Sardinian rural community from pre-industrial to modern time.

The oral microbial profile in humans has evolved in response to lifestyle changes over the course of different eras. Here, we investigated tooth lesions and the microbial profile of periodontal bacteria (PB) in dental calculus of a Sardinian pre-industrial rural community. In total, 51 teeth belonging to 12 historical individuals buried in an ossuary in the early 1800s and 26 modern teeth extracted from 26 individuals from the same geographical area were compared to determine the oral health status, bacterial load and amount of most relevant PB. Total caries and bacterial genomes count appeared to be sex-related in historical samples. Historical females presented a higher incidence of caries, PB pathogens and a higher bacterial load than historical males. Furthermore, we compared the PB profile of the historical individuals with the modern ones, revealing a notable increase in modern individuals of PB belonging to "Red complex bacteria" often associated with periodontitis and other chronic diseases of modern life. Our findings could be explained through an analysis of environmental factors such as socioeconomic, hygienic and healthy conditions that can have a great impact on oral health and bacterial composition among individuals of the same and different eras.

Evaluation of "Caterina assay": An Alternative Tool to the Commercialized Kits Used for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Identification.

Here we describe the first molecular test developed in the early stage of the pandemic to diagnose the first cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sardinian patients in February-March 2020, when diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The "Caterina assay" is a SYBR®Green real-time reverse-transcription polymerase chain reaction (rRT-PCR), designed to detect the nucleocapsid phosphoprotein (N) gene that exhibits high discriminative variation RNA sequence among bat and human coronaviruses. The molecular method was applied to detect SARS-CoV-2 in nasal swabs collected from 2110 suspected cases. The study article describes the first molecular test developed in the early stage of the declared pandemic to identify the coronavirus disease 2019 (COVID-19) in Sardinian patients in February-March 2020, when a diagnostic certified methodology had not yet been adopted by clinical microbiology laboratories. The assay presented high specificity and sensitivity (with a detection limit ≥50 viral genomes/µL). No false-positives were detected, as confirmed by the comparison with two certified commercial kits. Although other validated molecular methods are currently in use, the Caterina assay still represents a valid and low-cost detection procedure that could be applied in countries with limited economic resources.

Active Human and Porcine Serum Induce Competence for Genetic Transformation in the Emerging Zoonotic Pathogen Streptococcus suis.

The acquisition of novel genetic traits through natural competence is a strategy used by bacteria in microbe-rich environments where microbial competition, antibiotics, and host immune defenses threaten their survival. Here, we show that virulent strains of Streptococcus suis, an important zoonotic agent and porcine pathogen, become competent for genetic transformation with plasmid or linear DNA when cultured in active porcine and human serum. Competence was not induced in active fetal bovine serum, which contains less complement factors and immunoglobulins than adult serum and was strongly reduced in heat-treated or low-molecular weight fractions of active porcine serum. Late competence genes, encoding the uptake machinery for environmental DNA, were upregulated in the active serum. Competence development was independent of the early competence regulatory switch involving XIP and ComR, as well as sigma factor ComX, suggesting the presence of an alternative stress-induced pathway for regulation of the late competence genes required for DNA uptake.

Gait-cycle segmentation method based on lower-trunk acceleration signals and dynamic time warping.

Gait analysis is the systematic study of human walking. The analysis of gait signals from the lower trunk, acquired through accelerometers, begins with the proper identification of gait cycles. The goal of this work is to supplement gait-event based segmentation methods, tested for unimpaired and impaired populations, so that their need to calibrate or rely on pre-defined thresholds is overcome, and to implement strategies that reduce step-detection errors. A new system for the automatic extraction and analysis of gait cycles from acceleration signals of the lower trunk, combining knowledge from previous strategies with a dynamic time warping function, is presented. Performance was tested on gait signals from public databases. Sensitivities in step detection above 99.95% were achieved, with a positive predictive value of 100.00%. Step-correction strategies reduced the number of incorrect detections from 57 to 3 of 7056 steps. Bland-Altman plots and equivalence tests performed on cycle times by the proposed method and selected references showed good agreement, with mean differences below 0.003 s, and percent errors of 2%. This method may give place to a research tool for the automatic analysis of signals from subjects in a variety of cases.

In vitro Interactions between Streptococcus intermedius and Streptococcus salivarius K12 on a Titanium Cylindrical Surface.

Peri-implantitis is a steadily rising disease and is caused by oral bacterial pathogens able to form biofilm on implant surfaces and peri-implant tissues, making antibiotics treatment less effective. The use of commercial probiotics against oral pathogens could serve as an alternative to prevent biofilm formation. Streptococcus intermedius is one of the early colonizers of biofilm formation in dental implants. The aim of this study was to model the interaction between S. intermedius and Streptococcus salivarius strain K12, a probiotic bacterium producing bacteriocins. S. intermedius was co-cultured with S. salivarius K12 in an in vitro model simulating the biofilm formation in a dental implant composed by a titanium cylinder system. Biofilm formation rate was assessed by Real-Time PCR quantification of bacterial count and expression levels of luxS gene, used in response to cell density in the biofilm. Biofilm formation, bacteriocin production, luxS expression patterns were found to be already expressed within the first 12 h. More importantly, S. salivarius K12 was able to counter the biofilm formation in a titanium cylinder under the tested condition. In conclusion, our dental implant model may be useful for exploring probiotic-pathogen interaction to find an alternative to antibiotics for peri-implantitis treatment.

Estudio piloto sobre la utilización de la Estimulación Rítmica Auditiva empleando tango para mejorar la marcha y la calidad de vida en pacientes con Enfermedad de Parkinson que experimentan trastornos de la marcha / PILOT STUDY OF THE USE OF RHYTHMIC AUDITORY STIMULATION USING ARGENTINE TANGO, IN ORDER TO IMPROVE GAIT DISORDERS AND QUALITY OF LIFE, IN PARKINSON´S DISEASE PATIENTS

La Estimulación Rítmica Auditiva (ERA) es una técnica que facilita la rehabilitación de movimientos que son intrínseca y biológicamente rítmicos, como la marcha. Utiliza los efectos fisiológicos del ritmo auditivo sobre el sistema motor y funciona como un estímulo de sincronización y como facilitador para lograr patrones de marchas fisiológicos. El objetivo de este estudio piloto fue comparar los parámetros de marcha y calidad de vida antes y después de la implementación de ERA en pacientes con Enfermedad de Parkinson (EP) que sufrían trastornos de la marcha. Para el estudio se reclutaron 10 pacientes con EP "clínicamente establecida o probable" según criterios diagnósticos internacionales de entre 60 y 85 años de edad, con trastornos de la marcha leves. El entrenamiento con ERA duró 6 semanas y utilizó piezas de tango para sincronizar la marcha a rentes niveles de cadencia. Los resultados muestran una mejoría significativa de la marcha y el equilibrio (escala de Tinetti) luego del entrenamiento con ERA, la cual fue acompañada por una tendencia a la mejoría de la calidad de vida (escala PDQ-39). Estos resultados sugieren que la ERA fue capaz de mejorar la marcha y esto se tradujo en mejorías funcionales. Se requieren estudios aleatorizados, ciego y controlados en un mayor número de pacientes para continuar estudiando la potencial eficacia de la ERA

Rhythmic Auditory Stimulation (RAS) is a technique that facilitates the rehabilitation of movements that are intrinsically and biologically rhythmic, such as gait. It uses the physiological effects of perceived rhythm on the motor system and functions as a synchronization stimulus and as a facilitator to improved gait patterns. The objective of this pilot study was to compare gait parameters and quality of life before and after the implementation of RAS in patients with Parkinson's Disease (PD) with gait difficulties. For the study, 10 patients with clinically established or probable PD according to international diagnostic criteria, between 60 and 85 years of age, who suffered from mild gait disorders were recruited. Training with RAS lasted 6 weeks and used tango pieces to synchronize gait to different levels of cadence. The results show a significant improvement in gait and balance (Tinetti scale) after training with RAS, which was accompanied by a tendency to improve the quality of life (PDQ-39 scale). These results suggest that RAS was able to improve gait, which translated into functional improvements. Randomized, blinded, controlled trials in a larger number of patients are required to further assess the potential efficacy of RAS.

Evaluación de la adecuación del sistema de salud mental de Entre Ríos a la Ley Nacional de Salud Mental. Estudio de caso, 2018 / Evaluation of the adequacy of the mental health system of Entre Ríos to the Ley Nacional de Salud Mental Case study, 2018

INTRODUCCIÓN En 2010 Argentina promulga la Ley Nacional de Salud Mental que otorga un marco de legalidad a prácticas instituyentes sostenidas en la línea de la desmanicomialización. OBJETIVO Evaluar el estado de adecuación del sistema de salud mental de Entre Ríos a la ley N°26.657 en 2018, focalizando en un recorte del subsistema público; los cuatro hospitales monovalentes y los ocho hospitales generales con servicios de salud mental. MÉTODO Se llevó a cabo una investigación evaluativa. El diseño fue un estudio de caso único con unidades de análisis integradas y abordaje metodológico cuali-cuantitativo. La muestra fue no probabilística intencional utilizando fuentes primarias y secundarias. El proceso analítico se efectuó a lo largo de todo el proyecto; para los datos cuantitativos se aplicó estadística descriptiva mediante hoja de cálculo; los cualitativos se procesaron por segmentación de los textos e identificación de puntos claves en la data obtenida siguiendo como ejes las categorías teóricas planteadas. RESULTADOS Tanto para el eje de interdisciplina, intersectorialidad como para territorialidad, en la mitad de las instituciones relevadas se dieron indicadores de trabajo en este sentido, aunque no siempre fueron las mismas las que coincidieron en este avance en los mismos ejes, dando cuenta de la complejidad del campo. DISCUSIÓN En Entre Ríos se han dado movimientos en la línea de la adecuación a la LNSM a partir de una toma de posición tanto desde los niveles centrales de gestión como desde las micro gestiones de los dispositivos institucionales. Así como el territorio es heterogéneo y la distribución de recursos dispar, también se evidenciaron diferentes gradientes de adecuación. Los dispositivos que han logrado consolidar prácticas interdisciplinarias, intersectoriales y territoriales transmitieron un salto de calidad en la atención

Síndrome del cascanueces (nutcracker): una causa rara de dolor abdominal / Nutcracker syndrome: a rare cause of abdominal pain

No disponible

Human salivary peptide histatin-1 stimulates epithelial and endothelial cell adhesion and barrier function.

Histatins are multifunctional histidine-rich peptides secreted by the salivary glands and exclusively present in the saliva of higher primates, where they play a fundamental role in the protection of the oral cavity. Our previously published results demonstrated that histatin-1 (Hst1) promotes cell-substrate adhesion in various cell types and hinted that it could also be involved in cell-cell adhesion, a process of fundamental importance to epithelial and endothelial barriers. Here we explore the effects of Hst1 on cellular barrier function. We show that Hst1 improved endothelial barrier integrity, decreased its permeability for large molecules, and prevented translocation of bacteria across epithelial cell layers. These effects are mediated by the adherens junction protein E-cadherin (E-cad) and by the tight junction protein zonula occludens 1, as Hst1 increases the levels of zonula occludens 1 and of active E-cad. Hst1 may also promote epithelial differentiation as Hst1 induced transcription of the epithelial cell differentiation marker apolipoprotein A-IV (a downstream E-cad target). In addition, Hst1 counteracted the effects of epithelial-mesenchymal transition inducers on the outgrowth of oral cancer cell spheroids, suggesting that Hst1 affects processes that are implicated in cancer progression.-Van Dijk, I. A., Ferrando, M. L., van der Wijk, A.-E., Hoebe, R. A., Nazmi, K., de Jonge, W. J., Krawczyk, P. M., Bolscher, J. G. M., Veerman, E. C. I., Stap, J. Human salivary peptide histatin-1 stimulates epithelial and endothelial cell adhesion and barrier function.

Streptococcal Adhesin P (SadP) contributes to Streptococcus suis adhesion to the human intestinal epithelium.

BACKGROUND: Streptococcus suis is a zoonotic pathogen, causing meningitis and septicemia. We previously demonstrated that the gastrointestinal tract (GIT) is an entry site for zoonotic S. suis infection. Here we studied the contribution of Streptococcal adhesin Protein (SadP) to host-pathogen interaction at GIT level. METHODS: SadP expression in presence of Intestinal Epithelial Cells (IEC) was compared with expression of other virulence factors by measuring transcript levels using quantitative Real Time PCR (qRT-PCR). SadP variants were identified by phylogenetic analysis of complete DNA sequences. The interaction of SadP knockout and complementation mutants with IEC was tested in vitro. RESULTS: Expression of sadP was significantly increased in presence of IEC. Sequence analysis of 116 invasive strains revealed five SadP sequence variants, correlating with genotype. SadP1, present in zoonotic isolates of clonal complex 1, contributed to binding to both human and porcine IEC and translocation across human IEC. Antibodies against the globotriaosylceramide Gb3/CD77 receptor significantly inhibited adhesion to human IEC. CONCLUSION: SadP is involved in the host-pathogen interaction in the GIT. Differences between SadP variants may determine different affinities to the Gb3/CD77 host-receptor, contributing to variation in adhesion capacity to host IEC and thus to S. suis zoonotic potential.

European eel (Anguilla anguilla) plasma biochemistry alerts about propanil stress.

Propanil stress response in the eel (Anguilla anguilla) was examined. Eels were exposed to 3.16 mg/L for 72 hr and allowed to recover for 96 hr. Plasma levels of cortisol, lactate dehydrogenase (LDH), alkaline phosphatase (AP), aspartate aminotransferase (AST), cholesterol, triglycerides, glucose, ammonium, lactate, albumin, and total proteins as well as electrolytes (chloride, sodium, potassium, calcium and phosphorus) were determined. As a consequence of exposure, cortisol, AP, AST, and LDH increased. A hyperglycemic condition, together with hyperlactemia, hypoalbuminemia, hypoproteinemia, hypercholesterolemia and hypertriglycemia was registered. Ammonium increased during exposure concomitantly to hyponatremia, hypochloremia, hypocalcemia, hypophosphatemia, and hypokatremia. During recovery, chloride, sodium, potassium, ammonium, albumin and LDH normalized. At the end of the experiment, fish still exhibited hyperglycemia and hyperlactemia. Hypercalcemia was observed. Cholesterol, triglycerides, AP, and AST did not recuperate. These findings are important for assessing potential risks for areas where fish are grown near intensive herbicide use (i.e., paddy fields).

Effect of the lipid regulator Gemfibrozil in the Cladocera Daphnia magna at different temperatures.

In the present study, an ecotoxicological approach to the evaluation of Gemfibrozil (GEM) as an emerging organic pollutant was done. In order to assess its toxicity, tests were conducted using the cladocera Daphnia magna. Experiments were carried out at 22°C and 28°C. EC50, feeding behavior, and chronic toxicity tests (21 days) were evaluated in D. magna exposed to GEM as well as cholesterol levels at 21-day chronic exposure. D. magna GEM EC50 values (24 h) in our experimental conditions were 148.75 and 116.24 mg L-1 at 22°C and 28°C, respectively. Test concentrations of 0.1, 0.5, 1.0, 5.0 and 7.5 mg L-1 were selected for subacute and chronic experiments. Subacute short-term test (feeding study) was assessed after exposure to the toxicant. Filtration and ingestion rates of D. magna exposed animals did not show any significant difference (P > 0.05) with respect to control daphniids neither at 22°C nor at 28°C. Therefore, GEM test concentrations used in the present study did not reduce feeding behavior in D. magna. Temperature increased from 22°C to 28°C, which resulted in a decrease of the daphniids reproductive parameters such as brood size and number of young per female. Other parameters as longevity were not affected. The GEM concentrations used in the chronic test with D. magna did not affect daphniids longevity but some reproductive parameters as number of young per female or brood size were affected. Finally, a significant decreased in cholesterol levels was found in those animals exposed to the highest toxicant concentrations. More studies must be done to determine the possible implications of GEM in aquatic fauna and to derive its possible effects on the environment.

[Not Available]. / Efecto del tratamiento de dos días con orlistat sobre los niveles de leptina plasmática en pacientes obesas sin pérdida de peso.

Objetivo: poco se conoce sobre el impacto de orlistat en el sistema leptina. Estudiamos la respuesta de la leptina plasmática y la sensación de saciedad tras dos días de tratamiento con orlistat sin dieta hipocalórica ni pérdida de peso. Material y métodos: reclutamos veinte mujeres obesas en nuestras consultas externas de medicina. Habían recibido restricción dietética y modificación del estilo de vida, pero se habían mantenido obesas con peso corporal estable durante seis meses antes de su inclusión en el estudio. Resultados: las pacientes tomaron 120 mg de orlistat 3 veces al día y mantuvieron su dieta habitual. Al inicio y dos días después del tratamiento con orlistat se repitieron el examen físico, la sensación de hambre y la analítica. No hubo diferencias significativas en el consumo de energía de la dieta, el peso corporal y la relación cintura-cadera, así como en glucosa sérica, insulina y péptido C. Solamente las concentraciones de leptina y triglicéridos en suero disminuyeron (p: 0,0001 y 0,01, respectivamente). La disminución de la concentración de leptina en suero se correlacionó positivamente con cambios en la concentración de triglicéridos (p: 0.01, r2: 0,45). La sensación de hambre aumento antes de la cena y se correlacionó negativamente con la disminución de la leptina (p: 0,0001, r2: 0,74) y triglicéridos (p: 0,02, r2: 0.59). Conclusión: estos datos sugieren que la malabsorción parcial de grasas por el tratamiento con orlistat disminuye rápidamente los niveles plasmáticos de triglicéridos y leptina. Este descenso se asoció con aumento del apetito antes de la ingesta que sigue a la comida principal del día.

Effect of two days treatment with orlistat on plasma leptin in obese patients without weight loss / Efecto del tratamiento de dos días con orlistat sobre los niveles de leptina plasmática en pacientes obesas sin pérdida de peso

Objective: Little is known about the impact of orlistat on the leptin system. We studied the plasma leptin and satiety sensation response for two days of orlistat treatment without hypocaloric diet and weight loss. Material and methods: Twenty obese female subjects were recruited from our medical outpatient clinics. All of these subjects had previously received advice on dietary restriction and lifestyle modification, but remained obese with a stable body weight for at least six months before recruitment for the study. Results: Subjects were given 120 mg orlistat 3 times daily and were asked to maintain their usual diet. At baseline and two days after the treatment with orlistat, physical examination, hunger and blood analysis were repeated. There were no significant differences observed regarding energy dietary intake, body weight and waist-hip ratio, or in plasma glucose, insulin c-peptide concentrations. Only plasma leptin and triglycerides concentrations decreased (p: 0.0001 and 0.01 respectively). Decrease in plasma leptin concentration was positively correlated with changes observed in plasma triglycerides concentration (p: 0.01, r2: 0.45). Pre-dinner hunger increased and was negatively correlated with decrease in leptin (p: 0.0001, r2: 0.74) and triglycerides (p: 0.02, r2: 0.59). Conclusion: These data suggest that the partial fat malabsorption induced by the treatment with orlistat quickly reduces plasma triglycerides and leptin. This decrease is associated with increased appetite before intake following the main meal of the day (AU)

Objetivo: poco se conoce sobre el impacto de orlistat en el sistema leptina. Estudiamos la respuesta de la leptina plasmática y la sensación de saciedad tras dos días de tratamiento con orlistat sin dieta hipocalórica ni pérdida de peso. Material y métodos: reclutamos veinte mujeres obesas en nuestras consultas externas de medicina. Habían recibido restricción dietética y modificación del estilo de vida, pero se habían mantenido obesas con peso corporal estable durante seis meses antes de su inclusión en el estudio. Resultados: las pacientes tomaron 120 mg de orlistat 3 veces al día y mantuvieron su dieta habitual. Al inicio y dos días después del tratamiento con orlistat se repitieron el examen físico, la sensación de hambre y la analítica. No hubo diferencias significativas en el consumo de energía de la dieta, el peso corporal y la relación cintura-cadera, así como en glucosa sérica, insulina y péptido C. Solamente las concentraciones de leptina y triglicéridos en suero disminuyeron (p: 0,0001 y 0,01, respectivamente). La disminución de la concentración de leptina en suero se correlacionó positivamente con cambios en la concentración de triglicéridos (p: 0.01, r2: 0,45). La sensación de hambre aumento antes de la cena y se correlacionó negativamente con la disminución de la leptina (p: 0,0001, r2: 0,74) y triglicéridos (p: 0,02, r2: 0.59). Conclusión: estos datos sugieren que la malabsorción parcial de grasas por el tratamiento con orlistat disminuye rápidamente los niveles plasmáticos de triglicéridos y leptina. Este descenso se asoció con aumento del apetito antes de la ingesta que sigue a la comida principal del día (AU)

The effect of orlistat on postprandial hypertriglyceridemia by oral fat loading test. A systematic review / Efecto de orlistat sobre la hipertrigliceridemia posprandial valorada mediante el test de sobrecarga oral de grasas. Revisión sistemática

Orlistat induces weight loss by blocking hydrolysis of triglyceride in the intestine, and has thereby been associated with favorable changes in postprandial triglycerides (ppTGL). Some epidemiological studies have identified ppTGL concentrations as a significant risk factor for cardiovascular disease. Oral fat loading test (OFLT) has been used for screening of elevated levels of ppTGL. The objective of the present systematic review is to present available data on the effects of orlistat on OFLT. We found 11 studies, seven of which studied the effect of a single dose of orlistat on OFLT in three healthy volunteers, one with obesity, two with type-2 diabetes and one with hyperlipidemic patients. The other four studied the effect of orlistat on OFLT, but after a previous period of time with daily treatment with orlistat: 1 healthy volunteer, 2 obese volunteers, and one patient with hyperlipidemia. Our systematic review suggests that orlistat can help to reduce postprandial hypertriglyceridemia in obese, dyslipemic and type-2 diabetic patients. Regarding free fatty acids, they could be reduced but not all the authors have found the same results. In relation to type-2 diabetic patients, we have found three studies with conflicting results on the immediate effect of orlistat on the postprandial GLP-1 response. In conclusion, orlistat can help to reduce postprandial plasmatic TGL, especially in patients with postprandial hypertriglyceridemia related to obesity, dyslipidemia or type-2 diabetes (AU)

Orlistat induce la pérdida de peso mediante el bloqueo de la hidrólisis de triglicéridos en el intestino, por lo que también se asocia con cambios favorables en los triglicéridos posprandiales (PHTGL). Algunos estudios epidemiológicos han identificado concentraciones PHTGL como un importante factor de riesgo para la enfermedad cardiovascular. El test de sobrecarga oral de grasa (TSOG) se ha utilizado para la detección de niveles elevados de PHTGL. El objetivo de la presente revisión sistemática es presentar los datos disponibles sobre los efectos de orlistat en TSOG. Encontramos 11 estudios, de los cuales 7 estudian el efecto de una sola dosis de orlistat en el TSOG: 3 con voluntarios sanos, 1 con obesidad, 2 con diabetes de tipo 2 y 1 con pacientes hiperlipidémicos. Los otros 4 estudian también el efecto de orlistat en el TSOG, pero después de un periodo de tiempo previo con un tratamiento diario con orlistat: 1 con voluntarios sanos, 2 con obesidad y 1 con un paciente con hiperlipidemia. Nuestra revisión sistemática sugiere que orlistat puede ayudar a reducir la hipertrigliceridemia posprandial en pacientes obesos, dislipémicos y con diabetes de tipo 2. Respecto a los ácidos grasos libres plasmáticos, también los podría reducir, pero no todos los autores han encontrado los mismos resultados. En pacientes diabéticos de tipo 2 se han encontrado tres estudios con resultados contradictorios sobre el efecto inmediato de orlistat en la respuesta postprandial de GLP-1. En conclusión, orlistat puede ayudar a reducir los TGL plasmáticos posprandiales, especialmente en pacientes con hipertrigliceridemia posprandial relacionada con obesidad, dislipemia y diabetes de tipo 2 (AU)